Biomedical subjects

Anita Thapar

Publications and source records attributed to Anita Thapar.

At least 19 recordsLinked to original sources

PubMed2026

Stratifying the risk of transition to adult-onset psychiatric disorders in adolescents with anxiety.

BACKGROUND: Escalating mental health service demands have created a need to better identify young people most likely to require continued support from mental health services at the transition between childhood and adulthood. Anxiety is the most common adolescent mental health condition, yet its clinical significance and prognosis are not well understood. We aimed to examine the risk of young adult-onset psychiatric disorders in individuals with an adolescent anxiety disorder, and identify stratifiers of risk of subsequent psychiatric disorders in this group. METHODS: Individuals from the Norwegian Mother, Father, and Child Cohort Study (MoBa) with linked health records and aged 18 or over as of the 31st December 2023 were included. Those diagnosed with any ICD-10 anxiety disorder when aged 10-17 years were defined as having an adolescent anxiety disorder (n=2107, controls n=47,582). Polygenic scores (PGS) for psychiatric and neurodevelopmental conditions were calculated using LDpred2. Anxiety, comorbidities, and parental psychiatric history were defined through linked ICD-10 diagnoses. Sex was defined through linked records. Individuals were defined as having a young adult-onset psychiatric disorder if they first received any new psychiatric diagnosis aged 18-24. RESULTS: Adolescent anxiety diagnosis was associated with increased risk of all adult-onset psychiatric disorders (HR= 2.33-8.65). Post-traumatic stress disorder PGS, parental history of severe mental illness, and female sex were associated with increased risk of transition to a young adult-onset psychiatric disorder in people with an adolescent anxiety disorder. CONCLUSIONS: Adolescent anxiety greatly increases the risk of a psychiatric disorder during the transition to adult life. Clinicians should consider female sex and parental psychiatric history when prioritising young people with anxiety for adult mental health service support. Future research needs to further consider whether polygenic scores would aid risk stratification in clinical practice.

Norwegian Mother Father and Child Cohort Study↗

PubMed2026

Antecedents and outcomes of a later attention-deficit hyperactivity disorder (ADHD) diagnosis in females.

BACKGROUND: Females are less likely than males to be diagnosed with attention-deficit hyperactivity disorder (ADHD). When diagnosed, females are older than males. AIMS: In this study, we examined the childhood antecedents of later ADHD diagnosis and its impact on adolescent/emerging adult outcomes, with a focus on females. METHOD: In this cohort study, we used data from a Welsh nation-wide electronic cohort of 13 593 individuals (n = 2680 (19.7%) females) diagnosed with ADHD and 578 793 individuals (n = 286 734 (49.5%) females) without ADHD. We compared females with later diagnoses (ages 12-25) to those with earlier, timely diagnoses (ages 5-11) and no diagnosis, in terms of childhood (ages 5-11) antecedents and adolescent/adult (ages 12-25) outcomes. We also tested for sex differences. RESULTS: Although females with earlier ADHD diagnosis showed more health and educational difficulties in childhood than those with later diagnosed ADHD (odds ratios ranged from 0.18 to 0.92), there was clear evidence of these difficulties in females with later diagnosed ADHD, compared with females without ADHD (odds ratios: 1.07-9.02). In adolescence/early adulthood, females with later diagnosed ADHD used more healthcare services and had worse mental health, educational and socioeconomic outcomes than females diagnosed earlier (odds ratios: 1.39-4.96) and those without ADHD (odds ratios: 1.54-23.98). Many of these outcomes were exacerbated in females compared with males. CONCLUSIONS: The results demonstrate that later ADHD diagnosis is associated with significant negative outcomes by adolescence and disproportionately disadvantages females. Despite later diagnosis, there was clear evidence of childhood mental health and educational difficulties when compared with females without ADHD. Therefore, timely childhood ADHD diagnosis may help to mitigate later risks, especially for females.

Attention–deficit hyperactivity disorder↗

PubMed2025

Genome-wide association study of adolescent-onset depression.

Adolescent depression is a heritable psychiatric condition with rising global prevalence and severe long-term outcomes, yet its biological underpinnings remain poorly understood. We conducted the first genome-wide association study of adolescent-onset depression, comprising 102,428 cases (diagnosis or clinical symptom thresholds) and 286,911 controls, including diverse ancestries. Cross-ancestry meta-analysis identified 52 independent variants across 17 loci; European-only analysis found 61 variants at 29 loci, with a SNP-based heritability of 9.8%. Comparative analyses revealed two genes unique to adolescent-onset versus lifetime depression, enriched in neuronal subtypes, and two genes as potential drug repurposing targets. Polygenic scores were associated with adolescent-onset depression across ancestries, persistent depression trajectories, more severe outcomes, as well as reduced cortical volume, surface area and white matter integrity. Genetic correlation and Mendelian randomisation analyses support shared genetic liability and causal links with early puberty and modifiable health and behavioural risk factors. These findings uncover novel genetic loci and refine biological pathways underlying adolescent-onset depression, revealing age-specific mechanisms and early intervention opportunities.

Journal Article↗

PubMed2007

The association between conduct problems and the initiation and progression of marijuana use during adolescence: a genetic analysis across time.

The present study used a prospective, longitudinal design to investigate genetic and environmental influences on the association between earlier conduct problems and the initiation and progression of marijuana use during adolescence. Parent- and teacher-reported conduct problems assessed at Time 1 (1996) and self-reported marijuana use assessed at Time 2 (2004) were available for 1088 adolescent twin pairs participating in the Cardiff Study of All Wales and North West of England Twins (CaStANET). Using a novel approach to the modeling of initiation and progression dimensions in substance use, findings suggested that the initiation of marijuana use in adolescence was influenced by genetic, common and unique environmental factors. The progression (or frequency) of marijuana use was influenced by genetic and unique environmental factors. Findings for conduct problems indicated that while the presence or absence of conduct problems was largely heritable, the relative severity of conduct problems appeared to be more strongly environmentally influenced. Multivariate model fitting indicated that conduct problems in childhood and early adolescence made a small but significant contribution to the risk for marijuana use 8 years later.

Adolescent↗

PubMed2007

Gene-environment interplay in attention-deficit hyperactivity disorder and the importance of a developmental perspective.

Attention-deficit hyperactivity disorder (ADHD) varies in its clinical presentation and course. Susceptibility gene variants for ADHD and associated antisocial behaviour are being identified with emerging evidence of gene-environment interaction. Genes and environmental factors that influence the origins of disorder are not necessarily the same as those that contribute to its course and outcome.

Adolescent↗

PubMed2006

Agreement between maternal report and antenatal records for a range of pre and peri-natal factors: the influence of maternal and child characteristics.

BACKGROUND: Events during pregnancy and labour may influence the future health and well-being of offspring. Many studies rely on maternal reports of pre and peri-natal factors. Both maternal and child characteristics may potentially influence the reliability and accuracy of maternal recall. However, this has not been previously examined. AIMS: To examine agreement between information from maternally reported questionnaires and medical records for a range of pre and peri-natal factors. To examine whether maternal and child characteristics influence the level of agreement with medical records. METHODS: A survey of women who had school aged children born following in vitro fertilization (IVF) was carried out. Mothers completed a postal questionnaire booklet which included the Lewis and Murray scale which asks about antenatal and obstetric complications and the Strengths and Difficulties Questionnaire which assesses child behaviour problems. Antenatal case notes were also reviewed. Multi-centre ethical approval was obtained. Complete data were available for 126 women. RESULTS: The agreement between maternal report and medical records was very good for the majority of outcomes examined (infant birth weight, infant admission to special care baby unit, method of delivery, smoking during pregnancy, high blood pressure/oedema during pregnancy). Exceptions were length of labour and alcohol use during pregnancy. However, alcohol use during pregnancy was not routinely recorded in medical records. Maternal characteristics did not substantially influence level of agreement for the majority of outcomes examined. Exceptions were that agreement for length of labour was better in women with more educational qualifications and that agreement for pre-natal smoking was worse in women from higher socio-occupational groups. There was little evidence that child behaviour problems influenced the level of agreement between maternal recall and medical records. CONCLUSIONS: For the majority of pre and peri-natal events examined, mothers can provide accurate reports in comparison to information from medical records.

Alcohol Drinking↗

PubMed2006

The effect of birth-weight with genetic susceptibility on depressive symptoms in childhood and adolescence.

Low birth-weight has been associated with depression and related outcomes in adults, and with problem behaviours in children. This study aimed to examine the association between low birth-weight for gestation and depressive symptoms in children and adolescents and to examine whether the relationship is moderated by genetic risk for depression. An epidemiological, genetically sensitive design was used including 2,046 twins aged 8-17 years (1,023 families). Data were obtained by parental report and analysed using regression analysis. A small but significant association between birth-weight for gestation and early depressive symptoms was observed. The unit increase in depressive symptoms per unit decrease in birth-weight for gestation was greater for individuals at genetic or familial risk for depression. For low birth-weight children, genetic risk for depression moderated the influence of birth-weight for gestation in predicting early depressive symptoms. Birth-weight for gestation is moderated by genetic and familial risk for depression in influencing early depression symptoms. These observations have clinical implications in that the impact of being small for gestational age on depressive symptoms is greater in children at familial/genetic risk although the association between birth weight and depression does not imply causality.

Adolescent↗

PubMed2006

Predictors of antisocial behaviour in children with attention deficit hyperactivity disorder.

INTRODUCTION: Antisocial behaviour is an important adverse outcome of ADHD. The aim of this review is to examine what is known about the clinical, genetic and environmental factors that contribute to the link between ADHD and antisocial behaviour. METHODS: Electronic literature searches for the years 1980-2004 and examination of key reference books were undertaken. RESULTS: ADHD symptom severity and pervasiveness predict the development of antisocial behaviour. Genetic factors contribute substantially to the risk of developing both problems, although specific genes that influence the development of antisocial behaviour in ADHD have yet to be identified. Some of these genetic effects may be indirectly mediated through environmental risk (gene-environment correlation) or by increasing individual susceptibility to specific environmental adversity (gene-environment interaction). Antisocial behaviour in children with ADHD is also linked with family adversity as well as peer rejection, although some of this adversity may arise as a result of the child's symptoms. CONCLUSION: Despite the increased risk of antisocial outcomes in those with ADHD, relatively little is known about what risk factors and mechanisms contribute to the link between both these problems. Given the need for appropriate intervention and prevention strategies and targeting resources, more research is needed in this area.

Antisocial Personality Disorder↗

PubMed2006

Twin studies in pediatric depression.

Pediatric depression is an important clinical problem that is known to be familial. Twin studies have been used not only to examine the genetic etiology of depression but also to investigate developmental changes and gender effects, the relationship of depression with anxiety, and increasingly, the interplay of genetic liability with environmental risk factors. There is evidence that pediatric depression symptom scores and clinical depression are genetically influenced, but results from different twin studies have varied. These studies also have demonstrated the important contribution of environmental risk factors. Some of the differences in findings may be caused partly by clinical heterogeneity, developmental differences in etiology (stronger genetic influences for depression symptom scores in adolescence than in childhood), and measurement issues, such as who rates the symptoms.

Age Factors↗

PubMed2006

Family conflict interacts with genetic liability in predicting childhood and adolescent depression.

OBJECTIVE: To test for gene-environment interaction with depressive symptoms and family conflict. Specifically, to first examine whether the influence of family conflict in predicting depressive symptoms is increased in individuals at genetic risk of depression. Second, to test whether the genetic component of variance in depressive symptoms increases as levels of family conflict increase. METHOD: A longitudinal twin design was used. Children ages 5 to 16 were reassessed approximately 3 years later to test whether the influence of family conflict in predicting depressive symptoms varied according to genetic liability. The conflict subscale of the Family Environment Scale was used to assess family conflict and the Mood and Feelings Questionnaire was used to assess depressive symptoms. The response rate to the questionnaire at time 1 was 73% and 65% at time 2. Controlling for initial symptoms levels (i.e., internalizing at time 1), primary analyses were conducted using ordinary least-squares multiple regression. Structural equation models, using raw score maximum likelihood estimation, were also fit to the data for the purpose of model fit comparison. RESULTS: Results suggested significant gene-environment interaction specifically with depressive symptoms and family conflict. Genetic factors were of greater importance in the etiology of depressive symptoms where levels of family conflict were high. The effects of family conflict on depressive symptoms were greater in children and adolescents at genetic risk of depression. CONCLUSIONS: The present results suggest that children with a family history of depression may be at an increased risk of developing depressive symptoms in response to family conflict. Intervention programs that incorporate one or more family systems may be of benefit in alleviating the adverse effect of negative family factors on children.

Adolescent↗

PubMed2006

Relationship between disabling fatigue and depression in children: genetic study.

BACKGROUND: Medically unexplained disabling fatigue in young people is familial and frequently associated with depressed mood. AIMS: To examine the degree of sharing of genetic and environmental influences on the symptoms of depression and fatigue in this age group. METHOD: The parents of twins aged 8-17 years, derived from a population-based register, completed a questionnaire regarding lifetime-ever disabling fatigue in both twins. Twins aged 11 years or over completed the Mood and Feelings Questionnaire. The genetic and environmental influences on fatigue and the relationship with depression were examined using bivariate genetic analysis. RESULTS: Parent-rated data were obtained for 1468 twin pairs (65%) and self-rated data from 930 older twin pairs (58%). Bivariate analysis of fatigue and depression suggested that genetic and environmental influences on disabling fatigue were mainly specific to fatigue. CONCLUSIONS: Unexplained disabling fatigue in childhood is substantially familial and has mainly an independent aetiology from depression.

Adolescent↗

PubMed2005

The genetics of attention deficit hyperactivity disorder.

Attention deficit hyperactivity disorder (ADHD) is a highly heritable, disruptive, childhood-onset condition, the aetiology and pathogenesis of which is poorly understood. There have been relatively few genome-wide linkage studies, and no chromosomal region has yet been unequivocally implicated. In contrast, evidence from pharmacological, neuroimaging and animal studies has suggested the involvement of specific neurotransmitter systems, notably dopaminergic pathways, in ADHD and these aetiological clues have inspired a fruitful application of the candidate gene association approach. Meta-analyses or pooled data analyses have supported association between ADHD and polymorphisms in DRD4, DRD5 and SLC6A3 which encode dopamine D4 and D5 receptors and the dopamine transporter, respectively. A weaker, but nevertheless replicated, body of evidence also supports associations with SNAP-25 (synaptosomal-associated protein, 25 kDa) and SLC6A4 (serotonin transporter). There is increasing research interest in gene-phenotype links, clinical phenotypic markers of heterogeneity and gene--environment interaction, which are likely to be important in the next generation of genetic studies.

Attention Deficit Disorder with Hyperactivity↗

PubMed2005

The definition of disabling fatigue in children and adolescents.

BACKGROUND: Disabling fatigue is the main illness related reason for prolonged absence from school. Although there are accepted criteria for diagnosing chronic fatigue in adults, it remains uncertain as to how best to define disabling fatigue and Chronic Fatigue Syndrome (CFS) in children and adolescents. In this population-based study, the aim was to identify children who had experienced an episode of disabling fatigue and examine the clinical and demographic differences between those individuals who fulfilled a narrow definition of disabling fatigue and those who fulfilled broader definitions of disabling fatigue. METHODS: Participants (aged 8-17 years) were identified from a population-based twin register. Parent report was used to identify children who had ever experienced a period of disabling fatigue. Standardised telephone interviews were then conducted with the parents of these affected children. Data on clinical and demographic characteristics, including age of onset, gender, days per week affected, hours per day spent resting, absence from school, comorbidity with depression and a global measure of impairment due to the fatigue, were examined. A narrow definition was defined as a minimum of 6 months disabling fatigue plus at least 4 associated symptoms, which is comparable to the operational criteria for CFS in adults. Broader definitions included those with at least 3 months of disabling fatigue and 4 or more of the associated symptoms and those with simply a minimum of 3 months of disabling fatigue. Groups were mutually exclusive. RESULTS: Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were completed on 99 of the 129 participants (77%) who had experienced fatigue. There were no significant differences in demographic and clinical characteristics or levels of impairment between those who fulfilled the narrower definition and those who fulfilled the broader definitions. The only exception was the reported number of days per week that the child was affected by the fatigue. All groups demonstrated evidence of substantial impairment associated with the fatigue. CONCLUSION: Children and adolescents who do not fulfil the current narrow definition of CFS but do suffer from disabling fatigue show comparable and substantial impairment. In primary care settings, a broader definition of disabling fatigue would improve the identification of impaired children and adolescents who require support.

Adolescent↗

PubMed2005

Phenotypic variation between parent-offspring trios and non-trios in genetic studies of schizophrenia.

BACKGROUND: Phenotypic differences between parent-offspring trios and non-trios have been reported for various psychiatric disorders, and it has been suggested that this may make comparisons of case-control and family-based results for gene-disease association studies inappropriate. AIMS: To compare phenotypes between trios and non-trios with schizophrenia, and explore possible reasons for differences observed. METHOD: Phenotypes were compared between trios (n=75) and non-trios (n=424) collected as part of a case-control study. RESULTS: Differences were observed for most phenotypes investigated, although all were eliminated after adjusting for confounding. CONCLUSIONS: Confounding, genetic heterogeneity or selection bias could result in differences in case-control and family-based results. However as we discuss, where adequately designed case-control studies are used, gene-disease association results would be incomparable between family-based and case-control studies only if genetic heterogeneity was present. These results do not support the presence of such genetic heterogeneity in schizophrenia.

Adolescent↗

PubMed2005

A family based study implicates solute carrier family 1-member 3 (SLC1A3) gene in attention-deficit/hyperactivity disorder.

BACKGROUND: The glutamatergic system, the major excitatory neurotransmitter system in the central nervous system (CNS) has been proposed as contributing a possible role in the etiology of attention deficit hyperactivity disorder (ADHD). This is based upon observations from animal, neuroimaging, neuroanatomical and neuropsychological studies. Genes related to glutamate function are therefore good functional candidates for this disorder. The SLC1A3 (Solute Carrier Family 1, member 3) gene encodes a glial glutamate transporter which maps to chromosome 5p12, a region of linkage that coincides in two published ADHD genome scans so far. SLC1A3 is thus both a functional and positional candidate gene for ADHD. METHODS: We have undertaken detailed association analysis of SLC1A3 using a multi-stage approach for candidate gene analysis. RESULTS: In a family-based sample (n = 299) we found a significant association between marker rs2269272 (p = .007) and ADHD. Two, two-marker haplotypes, rs2269272/rs3776581 (p = .016) and rs2269272/rs2032893 (p = .013) also yielded evidence of association. CONCLUSIONS: The results of our study suggest that genetic variation in SLC1A3 may contribute to susceptibility to ADHD.

Adolescent↗

PubMed2005

Catechol O-methyltransferase gene variant and birth weight predict early-onset antisocial behavior in children with attention-deficit/hyperactivity disorder.

CONTEXT: Early-onset antisocial behavior accompanied by attention-deficit/hyperactivity disorder is a clinically severe variant of antisocial behavior that is associated with a particularly poor outcome. Identifying early predictors is thus important. Genetic and prenatal environmental risk factors and prefrontal cortical function are thought to contribute. Recent evidence suggests that prefrontal cortical function is influenced by a valine/methionine variant in the catechol O-methyltransferase (COMT) gene. OBJECTIVE: To test the a priori hypothesis that this genetic variant predicts early-onset antisocial behavior in a high-risk sample and further examine the effects of birth weight, an environmentally influenced index of prenatal adversity previously linked to childhood disruptive behaviors and genotype x birth weight interaction. DESIGN, SETTING, AND PARTICIPANTS: A family-based genetic study was undertaken between 1997 and 2003. Participants were prospectively recruited from child and adolescent psychiatry and child health clinics in the United Kingdom and included 240 clinic children who met diagnostic criteria for attention-deficit/hyperactivity disorder or hyperkinetic disorder. Participants underwent comprehensive standardized assessments including measures of antisocial behavior and IQ. Main Outcome Measure DSM-IV symptoms of childhood-onset conduct disorder rated by trained interviewers using a standard diagnostic interview. RESULTS: The results show main effects of the COMT gene variant (P = .002), birth weight (P = .002), and a significant gene x environment (COMT x birth weight) interaction (P = .006). CONCLUSIONS: Early-onset antisocial behavior in a high-risk clinical group is predicted by a specific COMT gene variant previously linked with prefrontal cortical function and birth weight, and those possessing the val/val genotype are more susceptible to the adverse effects of prenatal risk as indexed by lower birth weight.

Adolescent↗

PubMed2005

The Link between depression in mothers and offspring: an extended twin analysis.

Family studies have shown that maternal depression is a risk factor for depression in children. It is unclear, however, to what extent the familial transmission of depression from mother to child involves genes and how much is due to environmental adversity. This study used an extended twin design to assess the importance of environmental factors in the association of depression in mothers and children while simultaneously accounting for genetic relatedness in a UK. community sample of twins aged 8 to 17 years and their mothers. A model that constrained the genetic and environmental parameters to be equal within the two generations and included genetic and environmental paths between mother and offspring (twins) was tested with data from 1468 families. Significant environmental paths were found when maternal ratings were used. When cross-informant data were used (maternal depression and child self-reports of depression), the environmental path was no longer significant. However, for cross-informant data where children were classified as having high depression scores or scores within the normal range, significant environmental effects were found. These findings are interpreted in light of the strengths and weaknesses of the extended twin and other designs.

Adolescent↗

PubMed2005

Characterizing the ADHD phenotype for genetic studies.

The genetic study of ADHD has made considerable progress. Further developments in the field will be reliant in part on identifying the most appropriate phenotypes for genetic analysis. The use of both categorical and dimensional measures of symptoms related to ADHD has been productive. The use of multiple reporters is a valuable feature of the characterization of psychopathology in children. It is argued that the use of aggregated measures to characterize the ADHD phenotype, particularly to establish its pervasiveness, is desirable. The recognition of the multiple comorbidities of ADHD can help to isolate more specific genetic influences. In relation to both reading disability and conduct disorder there is evidence that genes may be involved in the comorbid condition that are different from pure ADHD. To date, progress with the investigation of endophenotypes for ADHD has been disappointing. It is suggested that extending such studies beyond cognitive underpinnings to include physiological and metabolic markers might facilitate progress.

Attention Deficit Disorder with Hyperactivity↗